Expression of Certain Leukemia/Lymphoma Related microRNAs and its Correlation with Prognosis in Childhood Acute Lymphoblastic Leukemia
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In spite of the improved efficacy of therapy, it still fails in 15–20 % of childhood acute lymphoblastic leukemia (ALL) patients. Recently, altered expression of certain miRNAs (miRs) have been described in ALL with potential effect on prognosis. Presence of certain miRs (miRNA-16, −21, −24, −29b, −128b, −142-3p, −155, −223) was characterized in human lymphoma and leukemia cells by real-time PCR. Expression of miRs in pediatric ALL patients (n = 24) was measured before chemotherapy, at conventional response checkpoints and at relapse. Correlation between altered miR expression and response to prednisolone at day 8 of therapy and long term prognosis was statistically analysed. Overexpression of “oncomiR/inflammamiR”-21 – which is characteristic in different tumors—was missing in human ALL cells. However, higher expression of miR-128b and lower expression of miR-223 is generally characteristic for human ALL cell lines and ALL cells isolated from pediatric patients. Correlation was shown between miR-128b expression and prognosis, prednisolone response and survival data in childhood ALL. Expression of miR-128b and miR-223—both are leukemia specific—changed in parallel with percentage of bone marrow blasts in remission and during relapse. Therefore, we suggest that overexpression of miR-128b and downregulation of miR-223 shows a significant correlation with treatment response and prognosis in childhood ALL.
KeywordsmiRNA-128b miRNA-223 Childhood ALL Prognosis Relapse
We thank Gézáné Csorba, András Weiperth, István Kenessey, Csaba Bödör, Tibor Füle, Hajnalka Rajnai for discussion and technical assistance. CCRF-CEM, Nalm6 and Mn60 ALL cell lines were a kind gift of Edit Buzás and Beáta Scholtz from cell culture laboratories at Semmelweis University, Budapest, and The Medical and Health Science Centre, University of Debrecen. The work was supported by Sebestyén A. and Kopper L. OTKA projects (K68341, K81624, K84262) of the Hungarian Academy of Sciences.
Conflict of interest
We declare that all authors have no financial or other conflict of interest that might bias their work.
- 13.Mi S, Lu J, Sun M, Li Z, Zhang H, Neilly MB, Wang Y, Qian Z, Jin J, Zhang Y, Bohlander SK, Le Beau MM, Larson RA, Golub TR, Rowley JD, Chen J (2007) MicroRNA expression signatures accurately discriminate acute lymphoblastic leukemia from acute myeloid leukemia. Proc Natl Acad Sci U S A 104:19971–19976CrossRefPubMedCentralPubMedGoogle Scholar
- 17.Löffler D, Brocke-Heinrich K, Pfeifer G, Stocsits C, Hackemüller J, Kretzschmar AK, Burger R, Gramatzki M, Blumert C, Bauer K, Cvijic H, Ullmann AK, Stadler PF, Horn F (2007) Interleukin-6 dependent survival of multiple myeloma cells involves the Stat3-mediated induction of microRNA-21 through a highly conserved enhancer. Blood 110:1330–1333CrossRefPubMedGoogle Scholar
- 22.Calin GA, Cimmino A, Fabbri M, Ferracin M, Wojcik SE, Shimizu M, Taccioli C, Zanesi N, Garzon R, Aqeilan RI, Alder RI, Alder H, Volinia S, Rassenti L, Liu X, Liu CG, Kipps TJ, Negrini M, Croce CM (2008) MiR-15a and miR-16-1 cluster functions in human leukemia. Proc Natl Acad Sci U S A 105:5166–5171CrossRefPubMedCentralPubMedGoogle Scholar
- 27.Lv M, Zhang X, Jia H, Li D, Zhang B, Zhang H, Hong M, Jiang T, Jiang Q, Lu J, Huang X, Huang B (2012) An oncogenic role of miR-142-3p in human T-cell acute lymphoblastic leukemia (T-ALL) by targeting glucocorticoid receptor-alpha and cAMP/PKA pathways. Leukemia 26:769–777CrossRefPubMedGoogle Scholar
- 30.Palumbo T, Faucz FR, Azevedo M, Xekouki P, Iliopoulos D, Stratakis CA (2013) Functional screen analysis reveals miR-26b and miR-128 as central regulators of pituitary somatomammotrophic tumor growth through activation of the PTEN-AKT pathway. Oncogene 32:1651–1659CrossRefPubMedCentralPubMedGoogle Scholar
- 42.Han BW, Feng DD, Li ZG, Luo XQ, Zhang H, Li XJ, Zhang XJ, Zheng LL, Zheng CW, Lin KY, Zhang P, Xu L, Chen YQ (2011) A set of miRNAs that involve in the pathways of drug resistance and leukemic stem-cell differentiation is associated with the risk of relapse and glucocorticoid response in childhood ALL. Hum Mol Genet 20:4903–4915CrossRefPubMedCentralPubMedGoogle Scholar
- 44.Alqurashi N, Hashimi SM, Wei MQ (2013) Chemical Inhibitors and microRNAs (miRNA) Targeting the Mammalian Target of Rapamycin (mTOR) Pathway: Potential for Novel Anticancer Therapeutics. Int J Mol Sci 14:3874–3900Google Scholar
- 45.Jia CY, Li HH, Zhu XC, Dong YW, Fu D, Zhao QL, Wu W, Wu XZ (2011) MiR-223 suppresses cell proliferation by targeting IGF-1R. PLoS One 6:e27008Google Scholar
- 48.Nemes K, Sebestyén A, Márk A, Hajdu M, Kenessey I, Sticz T, Nagy E, Barna G, Váradi Z, Kovács G, Kopper L, Csóka M (2013) Mammalian target of rapamycin (mTOR) activity dependent phospho-protein expression in childhood acute lymphoblastic leukemia (ALL). PLoS One 8:e59335CrossRefPubMedCentralPubMedGoogle Scholar